study to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of sapablursen (formerly isis 702843, ionis-tmprss6-lrx)

Conditions: Beta Thalassemia Intermedia

Summary: the purpose was to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of sapablursen administered subcutaneously to participants with non-transfusion dependent β-thalassemia intermedia.

this was a multi-center, randomized, open-label study in up to 29 participants. the duration of participation for each subject in the study was approximately 29 months and included an approximately 2-month screening period, a 24-month treatment period, and a 3-month post-treatment period.

Eligibility criteria:
inclusion criteria: * willingness to comply with study procedures * clinical diagnosis of beta-thalassemia intermedia with genotypic confirmation * non-transfusion dependent, as defined by: no more than 6 transfusions in the past 12-month period, and no transfusions in the 8-week period prior to day 1 * mean hb within the range of 6.0-10.0 g/dl, inclusive at screening * lic within the range of 3.0-20.0 mg fe/g dry weight, inclusive * if using chelators, must be on a stable dose for at least 3 months with liver iron concentration (lic) \> 5.0 mg iron (fe) per gram of dry weight of liver (fe/g) dry weight and serum ferritin \> 300 nanograms per milliliter (ng/ml) * females must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal * males must be surgically sterile, abstinent or using an acceptable contraceptive method exclusion criteria: * clinically significant abnormalities in lab values, medical history, or physical examination * α-globin gene triplication * symptomatic splenomegaly * platelet count \ 1,000 x 10\^9/l * significant concurrent/recent coagulopathy, history of non-traumatic significant bleeding; history of immune thrombocytopenic purpura (itp); current use of sc anti-coagulants; history of thrombotic events, including stroke or dvt * clinically significant renal, liver or cardiac dysfunction * uncontrolled hypertension (\> 140 mm hg systolic or \> 90 mm hg diastolic) * fasting blood glucose \> 2.0 × upper limit of normal (uln) * inability to have a magnetic resonance imaging (mri) scan * known history or positive test for human immunodeficiency virus (hiv), hepatitis c (hcv), or hepatitis b (hbv) * active infection requiring systemic antiviral or antimicrobial therapy * regular excessive use of alcohol * recent start of hydroxyurea (6 months prior to day 1) * treatment with or recent exposure to another investigational drug, biological agent, antisense oligonucleotide (aso), small interfering ribonucleic acid (sirna), or device within 1 month of screening, or 5 half-lives of investigational agent, whichever is longer; or treatment with or exposure to: * sotatercept (ace-011), luspatercept (ace-536), or ruxolitinib within 4 months of screening * hematopoietic stimulating agents or any hypoxia-inducible factor prolyl hydroxylase inhibitors within 8 weeks of day 1 * prior bone marrow transplant, stem cell transplant, or gene therapy * surgery associated with significant blood loss within 4 months of screening, splenectomy within 12 months of screening, or splenectomy scheduled during treatment

Keywords: thalassaemia beta thalassemia ionis tmprss6-lrx